AB0086 PORPHYROMONAS GULAE INFECTION IS NOT RELATED TO EXOGENOUS CITRULINATION OR DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS PATIENTS
Authors: C. Castellar, D. M. Castillo, L. Chila, W. Bautista-Molano, J. M. Bello-Gualtero, C. Romero-Sánchez
Journal: Annals of the Rheumatic Diseases (2022)

Background Porphyromonas gulae (P. gulae ) is a Gram negative microorganism of the Porphyromonadaceae family. It presents in its structure virulence factors similar to P. gingivalis , including the PAD enzyme. An enzyme responsible for catalyzing citrullination, related to the formation of autoantibodies against citrullinated peptides associated with Rheumatoid Arthritis (RA). Objectives To evaluate the presence of P. gulae and anti-citrullinated peptide antibodies of P. gulae PAD in patients with RA and their possible association with clinical markers of activity. Methods Ninety RA patients and 90 controls matched for age and sex were included. Serum levels of rheumatological markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-citrullinated protein antibodies (Anti-CCp/ACPA) and rheumatoid factor (RF) were measured. Disease activity was assessed using Disease Activity Indices-28 (DAS28) and SCDAI. The periodontal diagnosis was according to CDC and American Academy of Periodontology. The presence of P. gulae was established by qPCR, verifying the specificity and confirmed due to the high homology between P. gingivalis and P. gulae . The presence of antibodies against 2 peptides called VDK and LPQ were evaluated in their native structure and citrullinated at one end and inside the PPAD molecule of P.gulae. It was determined by ELISA in-house. Prediction of B and T epitopes of PPAD from P. gulae was made taking into account the location of arginines within the molecule, restricting it to HLA alleles associated with RA. Associations were established by Kruskal Wallis, Mann Whitney U tests and multiple correspondence discriminant analysis (MCDA) in SPSS V24 and STATA for Windows software, with a significance of 95%,p≤ 0.05. Results A frequency of P. gulae was observed in the RA group of 15.8% versus controls of 9.5%, p=0.1925, A Despite finding a diagnosis of periodontitis in 70.5% of the patients, it was not associated with clinical severity or diagnosis of periodontitis. Comparisons were made classifying the patients according to periodontal diagnosis, the presence of P. gulae was observed more frequently in the RA group with a diagnosis of periodontitis, compared to the control group (6.7% vs 2.5%, respectively) without statistical significance (p=0.2576). Of the 180 individuals evaluated, 17 had the presence of anti-citrullinated peptide antibodies of P. gulae PAD. Despite a higher frequency in the RA group of antibodies against two citrullinated peptides, the results were not significant (p=0.378 and p=0.346), there was no evidence of a relationship with activity or disease markers in RA. The MCDA test generated two dimensions, one with the clinical activity variables of RA with CC: 0.218, and a second dimension in which the presence of anti-citrullinated peptide antibodies of PAD CC were related to each other CC: 0.749; No positive correlation was found between the clinical variables of RA and the anti-citrullinated peptide antibodies of P. gulae PAD. Conclusion Despite the presence of P. gulae and PPAD citrullinated peptide antibodies from P. gulae in patients with RA, it was not possible to establish the relationship with clinical variables, which could indicate a lower contribution of this microorganismto the biological mechanism and molecular of citrullination common between RA and periodontitis. However, an additive effect of P. gulae with P. gingivalis in the citrullination process cannot be ruled out. Acknowledgements The Ministry of Science, Technology, and Innovation - MinCiencias (Grants No. 55642, 531734 and 740792). Universidad El Bosque (PCI-2018-10441), Hospital Militar Central and Fundación Instituto de Reumatología Fernando Chalem, in Bogota, Colombia. Disclosure of Interests None declared